ArticleMolecular psychiatry2021
GLP-1 receptor signaling in the laterodorsal tegmental nucleus attenuates cocaine seeking by activating GABAergic circuits that project to the VTA.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- The potential role of GLP-1 receptor agonists in substance use disorders - a systematic review.Frontiers in pharmacology · 2025Pooled it
- An Overview of Appetite-Regulatory Peptides in Addiction Processes; From Bench to Bed Side.Frontiers in neuroscience · 2021Pooled it
- Dorsomedial striatal GABA dynamics organize palatable reward consumption and are reshaped by GLP-1 receptor agonism.bioRxiv : the preprint server for biology · 2026Article
- GLP-1 Receptor Agonists and Substance Use Disorders in Older Adults With Type 2 Diabetes: A Target Trial Emulation.Obesity (Silver Spring, Md.) · 2026Observational
- Exendin-4 alleviates anxiety-like behaviors in chronic restraint stress miceActa pharmaceutica Sinica. B · 2026Article
- Glucagon-Like Peptide-1 Receptor Agonists in Cocaine Use Disorder: Clinical Observations and Underlying Mechanisms.Fundamental & clinical pharmacology · 2026Review
- Volitional cocaine taking engages distinct medium spiny neuron and astrocyte transcriptional programs in the rat nucleus accumbens.bioRxiv : the preprint server for biology · 2026Article
- Glucagon-like peptide-1 receptor agonist, semaglutide, attenuates intravenous self-administration of fentanyl in female rats.bioRxiv : the preprint server for biology · 2026Article
- Repurposing semaglutide as an adjunctive treatment for cocaine use disorder: protocol for a randomised controlled trial.BMJ open · 2026Article
- Tirzepatide attenuates mesolimbic cocaine-evoked dopamine levels and reduces cocaine taking, motivation and seeking behaviours in male rodents.EBioMedicine · 2026Article
- GLP-1 at the Metabolic-Cognitive Interface: Reward, Affect, and Memory.Comprehensive physiology · 2026Review
- Incretin-Based Therapies: A Novel Pathway in Addiction Treatment.Journal of clinical medicine · 2026Review
- GLP-1 Agonist Attenuates Nicotine Reward-Related Behavior by Regulating the Prepro-Orexin in the Hypothalamus and Prepro-Glucagon in the Nucleus Tractus Solitarius.Behavioural neurology · 2026Article
- Glucagon-like Peptide-1 receptor agonists as emerging therapeutics in bipolar disorder: a narrative review of preclinical and clinical evidence.Molecular psychiatry · 2026Review
- Glucagon-like peptide-1 medicines in neurological and psychiatric disorders.Cell reports. Medicine · 2025Review
- Neuroendocrinology meets addiction: Emerging pharmacotherapies on the horizon.Journal of internal medicine · 2025Review
- GLP-1 Therapeutics and Their Emerging Role in Alcohol and Substance Use Disorders: An Endocrinology Primer.Journal of the Endocrine Society · 2025Article
- Gastrointestinal Motility Effects of GLP-1 Receptor Agonists.Current gastroenterology reports · 2025Review
- GLP-1 Analogues in the Neurobiology of Addiction: Translational Insights and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- Emerging medications and pharmacological treatment approaches for substance use disorders.Pharmacology, biochemistry, and behavior · 2025Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
An emerging preclinical literature suggests that targeting central glucagon-like peptide-1 receptors (GLP-1Rs) may represent a novel approach to treating cocaine use disorder. However, the exact neural circuits and cell types that mediate the suppressive effects of GLP-1R agonists on cocaine-seeking behavior are largely unknown. The laterodorsal tegmental nucleus (LDTg) expresses GLP-1Rs and functions as a neuroanatomical hub connecting the nucleus tractus solitarius (NTS), the primary source of central GLP-1, with midbrain and forebrain nuclei known to regulate cocaine-seeking behavior. The goal of this study was to characterize the role of LDTg GLP-1R-expressing neurons and their projections to the ventral tegmental area (VTA) in the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we showed that administration of the GLP-1R agonist exendin-4 (Ex-4) directly into the LDTg significantly attenuated cocaine seeking at a dose that did not affect sucrose seeking, ad libitum food intake, or body weight. In addition, our studies revealed that selectively activating NTS-to-LDTg circuits attenuated cocaine seeking via a GLP-1R-dependent mechanism. We also demonstrated, for the first time, that GLP-1Rs are expressed primarily on GABAergic neurons in the LDTg and that the efficacy of Ex-4 to reduce cocaine seeking depends, in part, on activation of LDTg-to-VTA GABAergic projections. Taken together, these studies identify a central mechanism by which Ex-4 attenuates cocaine seeking and highlight GABAergic GLP-1R-expressing circuits in the midbrain as important anti-craving pathways in regulating cocaine craving-induced relapse.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.